{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Recent studies have begun to elucidate the multifunctional roles of the ERICH3 protein in human cells. One line of investigation has identified ERICH3 as an integral component of the primary cilium. Loss of ERICH3 in mammalian cells results in abnormally short cilia, with a concomitant accumulation of intraflagellar transport (IFT) proteins at the ciliary tip and reduced levels of retrograde transport regulators. These findings suggest that ERICH3 participates in retrograde IFT‐associated pathways that are critical for removing signaling molecules from the cilium, thereby maintaining proper ciliary structure and Sonic hedgehog pathway modulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In a separate set of investigations focusing on the central nervous system, ERICH3 has been shown to be highly expressed in neuronal cell types. Functional studies in serotonergic cells revealed that ERICH3 interacts with vesicular proteins, including clathrin heavy chain, and co‐localizes with serotonin and dopamine in vesicle-like structures. Disruption of ERICH3 expression—either through knockdown or via nonsynonymous single nucleotide polymorphisms that accelerate proteasome-mediated degradation—significantly reduces intracellular and secreted serotonin levels without altering the expression of enzymes that synthesize or metabolize serotonin. These data indicate that ERICH3 plays a pivotal role in vesicle function, affecting neurotransmitter storage and release, and may thereby modulate the clinical response to selective serotonin reuptake inhibitors."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Overall, these studies support a dual functional role for ERICH3: it is essential for the maintenance of ciliary integrity through regulation of retrograde IFT and, in parallel, it is critically involved in vesicular processes that influence serotonin and dopamine homeostasis. Such pleiotropic functions may underlie its association with diverse physiological processes, including cellular signaling pathways in the cilium and pharmacodynamic responses to antidepressant therapies.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Mona Alsolami, Stefanie Kuhns, Manal Alsulami, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ERICH3 in Primary Cilia Regulates Cilium Formation and the Localisations of Ciliary Transport and Sonic Hedgehog Signaling Proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-019-52830-1"}], "href": "https://doi.org/10.1038/s41598-019-52830-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31712586"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31712586"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Duan Liu, Yongxian Zhuang, Lingxin Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ERICH3: vesicular association and antidepressant treatment response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Psychiatry (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41380-020-00940-y"}], "href": "https://doi.org/10.1038/s41380-020-00940-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33230203"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33230203"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "M Gupta, D Neavin, D Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TSPAN5, ERICH3 and selective serotonin reuptake inhibitors in major depressive disorder: pharmacometabolomics-informed pharmacogenomics."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Psychiatry (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/mp.2016.6"}], "href": "https://doi.org/10.1038/mp.2016.6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26903268"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26903268"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Arjun P Athreya, Drew Neavin, Tania Carrillo-Roa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pharmacogenomics-Driven Prediction of Antidepressant Treatment Outcomes: A Machine-Learning Approach With Multi-trial Replication."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Pharmacol Ther (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cpt.1482"}], "href": "https://doi.org/10.1002/cpt.1482"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31012492"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31012492"}]}]}]}