FAM9B is an X-linked meiosis-associated protein localized to Xp22.3 that plays a critical role in male gametogenesis. Primary function: FAM9B localizes specifically to the synaptonemal complex (SC) region of primary spermatocytes and is co-localized with SYCP3, a key SC component, suggesting involvement in SC formation 1. The protein also co-localizes with γH2AX, a biomarker for DNA double-strand breaks, implicating FAM9B in meiotic DNA recombination 1. Mechanism: FAM9B is testis-exclusively expressed and localized to spermatocyte nuclei 2. The protein shows homology to SYCP3, a synaptonemal complex component 2. Disease relevance: FAM9B variants are associated with nonobstructive azoospermia (NOA), with potential loss-of-function variants identified in infertile men 34. However, recent evidence suggests FAM9B loss-of-function variants also occur in fertile males, indicating monogenic causation may be limited 4. Clinical significance: A genetic variant near FAM9B (rs5934505) shows association with serum testosterone concentrations in men 5. Additionally, FAM9B variants show male-specific genetic effects on kidney function traits 6, and a locus containing FAM9B demonstrates male-specific inguinal hernia susceptibility 7.