ATP2C2 encodes a P-type ATPase that transports calcium and manganese ions into the Golgi apparatus lumen, where these cofactors are essential for protein processing and secretory pathway trafficking. The pump acquires these ions on the cytoplasmic side and delivers them to the lumenal side via ATP-driven conformational changes [UniProt Function]. Beyond its canonical pump function, ATP2C2 also mediates store-independent calcium influx at the plasma membrane through interaction with the calcium channel ORAI1, facilitating calcium entry independently of endoplasmic reticulum or Golgi stores [UniProt Function]. In mammary epithelial cells, this dual mechanism may support transepithelial calcium transport for milk secretion [UniProt Function]. ATP2C2 variants are associated with developmental language impairment. Genome-wide association studies identified common variants linked to phonological short-term memory deficits in specific language impairment cohorts 1, and a rare missense variant was found more frequently in language-impaired children (1.8%) than in dyslexia or ADHD cohorts or general population controls 2. A de novo deletion encompassing ATP2C2 caused global language impairment in a patient with intact hearing and normal neurological development otherwise 3. These findings suggest ATP2C2 contributes to neurodevelopmental pathways underlying language acquisition 4. Emerging evidence indicates ATP2C2 may also influence breast cancer tumor microenvironment composition, with higher expression correlating with reduced survival 5. ATP2C2 variants are additionally associated with age at cannabis initiation 6, and the gene's calcium-signaling role implicates it in substance use pathways 7.