Pantothenate kinase 1 (PANK1)

Pantothenate kinase 1 (PANK1) is an enzyme that catalyzes the first and rate-limiting step in coenzyme A biosynthesis by converting pantothenic acid to 4'-phosphopantothenate. It plays a crucial role in cellular metabolism and energy homeostasis, regulating the acetyl-CoA/CoA ratio necessary for fatty acid metabolism, the citric acid cycle, and protein acetylation. PANK1 exerts additional biological functions as a negative regulator of Wnt/β-catenin signaling via cooperative phosphorylation of β-catenin (with CK1α), impacting cell growth and cancer progression. It is tightly regulated both by metabolic products (feedback inhibition by CoA and its thioesters) and at the transcriptional level by the tumor suppressor p53. Dysfunction or altered expression of PANK1 is implicated in cancer, neurodegeneration, and metabolic syndromes.

Other names

Pantothenate kinase 1PANK1PANKhPanKhPanK1MGC24596PANK1aPANK1bPantothenic acid kinase 1

Drugs may target the kinase activity to modulate CoA biosynthesis or β-catenin stability (e.g., inhibition suppresses phosphorylation of β-catenin, affects Wnt/β-catenin signaling). CoA thioesters exert feedback inhibition; drugs that mimic this mechanism can regulate its activity.