SAT2 encodes a member of the spermidine/spermine N1-acetyltransferase family that catalyzes N-acetylation of thialysine, a structural lysine analog. While SAT2 may also acetylate polyamines such as norspermidine, spermidine, and spermine, this polyamine acetyltransferase activity appears weak, suggesting limited in vivo diamine acetyltransferase function. SAT2 plays a developmental role in testicular cord formation and Sertoli cell–germline interactions during neonatal testicular development. The protein binds and represses STIM1 expression, thereby modulating reactive oxygen species and WNT/β-catenin signaling pathways critical for spermatogonial stem cell maintenance 1. Dysregulation of SAT2 impairs Sertoli cell migration and positioning, leading to defects in germ cell support. Genome-wide association studies identify SAT2 as a plasma protein mediating the causal relationship between smoking and essential hypertension 2. Additionally, SAT2 shows nominal association with diabetes-related traits in the context of dietary-induced metabolic stress 3. At the epigenetic level, changes in Sat2 methylation occur in prostatic preneoplastic lesions and are associated with breast cancer development, with hypomethylation of Sat2 satellite DNA serving as an early biomarker of cancer even at low tumor grades 4, 5.