SPA17 (sperm autoantigenic protein 17) is a conserved mammalian protein primarily characterized as a sperm surface zona pellucida binding protein that facilitates spermatozoa attachment with high affinity. In reproductive physiology, SPA17 localizes to the sperm principal piece and ciliary structures 1, where it participates in the acrosome reaction during fertilization 2. The protein functions through interactions with A-kinase-anchoring proteins (AKAPs) and PKA signaling; oxidative stress-induced elevation of SPA17 inhibits sperm capacitation and reduces acrosomal reactions by suppressing AKAP4/PKARII protein expression 3. Beyond reproduction, SPA17 has emerged as a cancer-testis antigen (CTA) aberrantly expressed in multiple malignancies 2. Pan-cancer analysis reveals SPA17 predicts prognosis across cancer types and significantly correlates with immune cell infiltration and immune-activated hallmarks 2. Notably, SPA17 expression predicts anti-PD1/PDL1 immunotherapy response, positioning it as a promising immunotherapy biomarker 2. In pancreatic ductal adenocarcinoma, SPA17 contributes to a biomarker panel distinguishing chemotherapy responders (AUROC: 0.977) 4. Recently, SPA17 has been identified as a pan-interstitial lung disease (ILD) marker correlating positively with disease severity and lung function progression in systemic sclerosis-associated ILD and idiopathic pulmonary fibrosis 5.