Hyccin PI4KA lipid kinase complex subunit 1 (HYCC1)

Hyccin PI4KA lipid kinase complex subunit 1 (HYCC1), also known as FAM126A or hyccin, is a regulatory protein essential for the localization and activity of the PI4KIIIα (phosphatidylinositol 4-kinase alpha) lipid kinase complex at the plasma membrane[1][2][3][6]. This complex catalyzes the first committed step in the synthesis of phosphatidylinositol-4-phosphate (PI4P), a precursor for major phosphoinositides that control membrane identity, signal transduction, and cellular homeostasis[2][6][8]. HYCC1 is especially vital for myelination, influencing oligodendrocyte differentiation and nervous system function[1][3][9]. Genetic defects cause hypomyelinating leukodystrophy type 5 (HLD5), characterized by severe neurodevelopmental impairment and, in some cases, congenital cataracts[3][5][9]. As a member of the PI4K complex, HYCC1 is a therapeutic target in rare genetic diseases, and PI4KIIIα inhibitors interact with the assembled kinase complex; however, no direct drugs targeting HYCC1 are currently approved[2][8]. Disruption of its function leads to profound cellular and organismal defects, underscoring its importance in membrane phosphoinositide homeostasis and neural biology[8][9].

Other names

FAM126AhyccinDRCTNNB1AHCCDown-regulated by CTNNB1 protein Adown regulated by Ctnnb1family with sequence similarity 126 member AHYCC1HLD5

Inhibitors targeting PI4KIIIα enzymatic site block phosphoinositide synthesis by preventing PI phosphorylation; regulatory subunit disruption impairs kinase targeting and myelination