Ip6k3, Inositol hexakisphosphate kinase 3, is an enzyme that generates inositol pyrophosphates. These molecules regulate diverse cellular functions and are involved in pathways such as energy sensing, with implications for processes like metabolism and neuronal function [1,2,4]. Genetic models, especially KO mouse models, have been crucial in studying its functions.

Ip6k3 -/- mice showed lower blood glucose, reduced fat mass, increased plasma lactate, enhanced glucose tolerance, and extended lifespan, indicating its role in metabolic control and lifespan regulation [1]. IP6K3 is highly concentrated in cerebellar Purkinje cells. Its deletion led to abnormalities in Purkinje cell structure, synapse number, and motor learning and coordination deficits, suggesting it is a determinant of cytoskeletal disposition and function in these cells [3]. Also, IP6K3 knockout decreased the amount of vesicular glutamate transporters in the readily releasable pool, affecting synaptic facilitation, pointing to its role in synaptic vesicle recycling [5].

Deletion of Ip6k3 also protected mice from age-induced fat accumulation and insulin resistance, highlighting its role in metabolic diseases [6]. And knockout of IP6K3 caused defects in cell motility and neuronal dendritic growth, leading to brain malformations, showing its role in focal adhesion turnover [7].

In conclusion, Ip6k3 plays essential roles in metabolic regulation, lifespan determination, synaptic function, and cell motility. Studies using KO mouse models have revealed its significance in metabolic diseases and neurological conditions, providing insights into the underlying mechanisms and potential therapeutic targets.