ARMC3 (armadillo repeat containing 3) is essential for male fertility through its role in regulating autophagy during spermatogenesis. As the mammalian homolog of yeast Vac8, ARMC3 functions in anchoring phosphatidylinositol 3-kinase (PIK3C3-C1) at the phagophore assembly site to initiate autophagy 1. Specifically, ARMC3 promotes ribophagy—the selective autophagic degradation of cytosolic ribosomes—in developing spermatids, which provides essential energy resources for mitochondria and ensures flagellar motility 1. The protein contains conserved armadillo repeat domains and exists as multiple splicing variants with tissue-specific expression patterns 2. Loss-of-function mutations in ARMC3 cause complete male infertility characterized by asthenozoospermia (reduced sperm motility) and flagellar disorganization, including vacuolation in mitochondria and disrupted ultrastructure of the flagellar principal and end pieces 3. Beyond reproductive function, ARMC3 mutations have been associated with non-syndromic stuttering, suggesting neurodevelopmental roles 4. Additionally, ARMC3 genetic variants show associations with variation in Epstein-Barr virus antibody responses and autoimmune disease susceptibility 5. ARMC3 interacts functionally with other spermatogenesis-related proteins including MYCBPAP 6, highlighting its role in the multi-protein regulatory networks essential for male fertility.