{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nLeucine‐rich repeat kinase 1 (LRRK1) is a multifunctional regulator of cellular homeostasis with crucial roles in the central nervous system. In the aging brain, LRRK1, in collaboration with its homolog LRRK2, is essential for the survival of dopaminergic neurons, with its loss leading to age‐dependent neurodegeneration that is associated with increased apoptosis and accumulation of autophagic vacuoles. LRRK1 is further implicated in the regulation of autophagic flux, where it is recruited to autolysosomes to modulate Rab7 activity—effectively switching off Rab7 signaling—and phosphorylates Rab7A at Ser72, thereby fine‐tuning endosomal trafficking and degradation pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the skeletal system, LRRK1 plays a critical role in osteoclast function and bone remodeling. Disruption of LRRK1 leads to severe osteopetrosis, which is attributed to defective osteoclast cytoskeletal organization and reduced bone resorption. Mechanistic studies reveal that LRRK1 governs signaling cascades involving c‐Src and the small GTPases RAC1/Cdc42, and modulates actin assembly through targets such as L‑plastin, ensuring the formation of functional resorptive structures."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in autophagy and skeletal remodeling, LRRK1 is integral to immune cell signaling and epithelial function. In B cells, LRRK1 enhances B‑cell receptor–mediated NF‑κB activation, thereby promoting the expression of genes vital for cell proliferation, survival, and class‐switch recombination during humoral immune responses. Concurrently, LRRK1 interacts with factor inhibiting hypoxia‑inducible factor 1 (FIH‑1) to modulate epidermal growth factor receptor (EGFR) trafficking and signaling, a process that underpins keratinocyte migration and effective wound healing."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Emilie Giaime, Youren Tong, Lisa K Wagner, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Leucine-Rich Repeat Kinase 1 Regulates Autophagy through Turning On TBC1D2-Dependent Rab7 Inactivation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00085-15"}], "href": "https://doi.org/10.1128/MCB.00085-15"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26100023"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26100023"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Asad U Malik, Athanasios Karapetsas, Raja S Nirujogi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deciphering the LRRK code: LRRK1 and LRRK2 phosphorylate distinct Rab proteins and are regulated by diverse mechanisms."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BCJ20200937"}], "href": "https://doi.org/10.1042/BCJ20200937"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33459343"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33459343"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Weirong Xing, Jeff Liu, Shaohong Cheng, et al. 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