ATP2C1 encodes a P-type ATPase that pumps calcium and manganese ions from the cytoplasm into the Golgi apparatus lumen in an ATP-dependent manner 123. The pump operates through a catalytic cycle involving transient phosphorylation that shifts the protein between inward-facing and outward-facing conformational states, facilitating ion translocation across the membrane 24. ATP2C1 maintains Golgi calcium homeostasis, which is essential for protein processing, trafficking, and proper cisternae morphology 53. In keratinocytes specifically, ATP2C1 loads Golgi calcium stores, supporting keratinocyte differentiation and epidermis integrity 65. Heterozygous mutations in ATP2C1 cause Hailey-Hailey disease, a rare autosomal dominant acantholytic dermatosis characterized by compromised keratinocyte adhesion, vesico-bullous lesions in friction areas, and abnormal cytosolic calcium/manganese levels 78. Over 166 pathogenic ATP2C1 mutations have been identified globally, including frameshift and nonsense variants 9. Disease manifestations result from altered junctional protein synthesis and acantholysis, with clinical severity influenced by environmental triggers including humidity, friction, and heat 7. Currently, no cure exists; management involves symptom control through topical and systemic therapies 7.