ANO9 (anoctamin 9) is a multifunctional membrane protein that operates as a PKA-activated nonselective cation channel with poor cation discrimination but preferential Ca2+ permeability 1. The protein functions as a calcium-activated calcium permeable channel that may operate as an endoplasmic reticulum Ca2+-leak channel, reducing ER Ca2+ store loading and regulating intracellular Ca2+ signals in renal tissue 2. ANO9 exhibits calcium-dependent phospholipid scramblase activity, scrambling phosphatidylserine, phosphatidylcholine and galactosylceramide across cell membranes 3. In T-cell activation, ANO9 is essential for the initial rise in intracellular Ca2+ through store-operated ORAI1 Ca2+ entry channels and recruits Ca2+-ATPase to the plasma membrane to maintain proper Ca2+ signaling 2. ANO9 has significant disease relevance, with rare loss-of-function mutations being depleted in centenarians, suggesting a role in longevity 4. In cancer, ANO9 expression correlates with tumor progression, with decreased expression associated with poor prognosis in colorectal cancer 5 and regulation of immune checkpoint protein PD-L2 expression in gastric cancer 6. ANO9 has also been identified as a potential risk gene for frontotemporal lobar degeneration and idiopathic pulmonary fibrosis 78.