LRGUK (leucine rich repeats and guanylate kinase domain containing) is a critical regulator of male germ cell development with primary functions in sperm morphogenesis and fertility. The protein mediates multiple aspects of spermatogenesis, including acrosome attachment, sperm head shaping, and axoneme initiation 1. LRGUK-1 functions as a major determinant of microtubule structure by regulating basal body attachment to the plasma membrane, sub-distal appendage formation, axoneme microtubule extension, and microtubule organization within the manchette 1. Mechanistically, LRGUK-1 operates within a multiprotein complex involving HOOK family proteins, RIMBP3, and kinesin light chain-3, with its guanylate kinase-like domain essential for binding HOOK2 and RIMBP3, and its leucine-rich repeat domain essential for KLC3 binding 2. Mutations in LRGUK cause male infertility in humans, with recessive variants identified in infertile males with abnormal sperm morphology and reduced sperm output 3. Additionally, polymorphisms near LRGUK on chromosome 7 show association with Type 2 diabetes and fasting glucose levels, suggesting roles beyond reproduction 4. The gene's expression is dysregulated in nonobstructive azoospermia, where long noncoding RNA LINC00467 regulates LRGUK expression, implicating lncRNA-mediated mechanisms in male infertility pathogenesis 5.