AbstractThe sperm annulus, a septin‐based ring structure, is important for reproductive physiology. It is composed of SEPT12‐based septin core complex followed by assembling as octameric filament. In clinical examinations, mutations of Septin12 result in male infertility, immotile sperm, as well as sperm with defective annuli. The dynamic assembly of septin filaments is regulated by several post‐translational modifications, including sumoylation, acetylation, and phosphorylation. Here, we briefly review the biological significance and the regulation of SEPT12 phosphorylation in the mammalian sperm physiology. During mammalian spermiogenesis, the phosphorylation of SEPT12 on Ser198 residue is important in regulating mammalian annulus architectures. SEPT12 phosphomimetic knock‐in mice displayed poor male fertility due to weak sperm motility and loss of the sperm annulus. SEPT12 is phosphorylated via Protein kinase A (PKA), and its phosphorylation interfered with SEPT12 polymerization into complexes and filaments. Taken together, the phosphorylation status of SEPT12 is crucial for its function in regulating the mammalian sperm physiology.