Diphosphoinositol pentakisphosphate kinase 1 (PPIP5K1)

Diphosphoinositol pentakisphosphate kinase 1 (PPIP5K1) is a bifunctional enzyme with both kinase and phosphatase activity involved in the synthesis and breakdown of inositol pyrophosphates, specifically phosphorylating inositol hexakisphosphate (InsP6) and diphosphoinositol pentakisphosphate (PP-InsP5) to generate critical signaling molecules such as InsP7 and InsP8[3][1][2]. These inositol pyrophosphates regulate diverse cellular processes, including apoptosis, cytoskeletal dynamics, vesicle trafficking, insulin signaling, and immune cell function[3][2]. The enzyme uniquely combines a kinase domain (N-terminal) and a phosphatase domain (C-terminal), allowing it to catalyze both the formation and degradation of inositol pyrophosphates via a "futile cycle"[2][1]. PPIP5K1 activity is regulated by cellular nutrient status and signaling pathways such as PI3-kinase, and translocates in response to receptor activation[5]. Disruption of PPIP5K1 function has implications for human diseases including cancer, diabetes, and inflammation[3][2]. There are no known drugs currently targeting PPIP5K1 specifically, and its extensive roles in cellular signalling suggest therapeutic targeting would pose significant challenges in safety and systemic effects.

Other names

Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 1HISPPD2AIP6KIPS1VIP1hsVIP1KIAA0377Inositol pyrophosphate synthase 1InsP6 and PP-IP5 kinase 1DIPPShistidine acid phosphatase domain-containing protein 2A