LY6G5C (lymphocyte antigen 6 family member G5C) is a cysteine-rich protein encoded in the MHC class III region that may play roles in hematopoietic cell differentiation and epididymal sperm maturation. Structurally, LY6G5C is likely a secreted protein rather than a GPI-anchored cell surface protein, distinguishing it from related Ly-6 family members 1. The protein's potential ligands are expressed on undifferentiated megakaryocytes, suggesting involvement in hematopoietic differentiation 1. In male fertility, LY6G5C (together with Ly6g5b) is essential for sperm maturation; knockout mice showed subfertility with reduced sperm ADAM3 levels, a protein critical for zona pellucida binding 2. Beyond reproduction, altered LY6G5C methylation has been associated with multiple conditions. Differential methylation near LY6G5C was identified in epigenome-wide association studies of pancreatic cancer 3, fibromyalgia syndrome 4, schizophrenia 5, and migraine as a novel pathophysiological factor 6. These epigenetic alterations suggest LY6G5C may contribute to disease susceptibility through immune and cellular signaling pathways, though direct molecular mechanisms remain incompletely characterized.