ALPL encodes a tissue non-specific alkaline phosphatase, a key enzyme in ectopic calcification, whose overactivity in VSMCs and macrophages promotes aortic valve calcification, and cardiac fibrosis through pathways like TGF-β1/Smads, ERK1/2, and p53 [30,31,32,33]. The gene discussed is MAPK3; the disease is fibrosis.