{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSUN5 is a testis‐specific nuclear envelope protein that localizes precisely at the sperm head–tail junction, and its proper function is indispensable for the integration of the sperm head with its tail. Loss‐of‐function mutations—including missense, frameshift, splice‐site, and large deletion variants—lead to the production of truncated or mislocalized SUN5 protein, resulting in acephalic spermatozoa syndrome and consequent male infertility. These findings have been documented in several studies where genetically affected individuals exhibited a high prevalence of headless or decaudated spermatozoa."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its essential role in head–tail attachment, mechanistic investigations have revealed that SUN5 interacts with key proteins involved in spermatogenesis. For example, SUN5 has been shown to bind with the co-chaperone DNAJB13, and its proper folding and cellular distribution are critical for the stabilization of this interaction. Moreover, studies in Sun5 knockout mice have identified partners such as the nuclear envelope protein LaminB1 and cytoskeletal GTPases like Septin12, which cooperate to secure the proximal centriole to the nucleus, thereby maintaining the structural integrity of the sperm neck."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThe genetic spectrum of SUN5 mutations is broad, with diverse allelic variants disrupting protein expression and localization. Experimental evidence from multiple cohorts has demonstrated that such mutations frequently hinder the proper distribution of associated proteins (e.g., ODF1) and culminate in the characteristic decapitated or headless sperm phenotype observed in acephalic spermatozoa syndrome. Detailed analyses have confirmed that various loss-of-function alleles, including homozygous frameshift and compound heterozygous variants, directly impair SUN5 function, reinforcing its critical role in sperm head–tail connectivity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurthermore, studies of related SUN domain–containing proteins, such as SPAG4L, underscore the broader significance of the SUN protein family in maintaining nuclear envelope integrity and facilitating key events during spermatogenesis. Although SPAG4L displays a distinct expression pattern, these findings collectively reinforce the concept that proper organization of SUN domain proteins is essential for normal nuclear and cellular architecture during germ cell development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Fuxi Zhu, Fengsong Wang, Xiaoyu Yang, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "SUN5 interacts with nuclear membrane LaminB1 and cytoskeletal GTPase Septin12 mediating the sperm head-and-tail junction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Hum Reprod (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/molehr/gaae022"}], "href": "https://doi.org/10.1093/molehr/gaae022"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38870534"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38870534"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yan-Wei Sha, Xiaohui Xu, Zhi-Yong Ji, et al. 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