PIK3C2B, encoding for the class II phosphatidylinositol 3-kinase PI3K-C2β, is involved in lipid signalling and phosphoinositide (PIP) metabolism. It phosphorylates intracellular inositol lipids to regulate signalling and intracellular vesicular trafficking, and is associated with pathways such as the AKT/mTOR pathway [1,2,4].

In myotubular myopathy (MTM) animal models, muscle-specific ablation of Pik3c2b completely prevented the MTM phenotype, and postsymptomatic targeting promoted a remarkable rescue of the disease, suggesting Pik3c2b is a genetic modifier of Mtm1 mutation [3].

In focal epilepsy, heterozygous ultra-rare variants in PIK3C2B act as loss-of-function alleles, leading to impaired synthesis of phosphatidylinositol 3,4-bisphosphate, mTORC1 hyperactivation, neuronal hyperexcitability and increased seizure susceptibility, indicating haploinsufficiency as a key driver of the disease [2].

In age-related macular degeneration, ALKBH5 targets PIK3C2B and regulates the AKT/mTOR signalling pathway, contributing to retinal pigment epithelium anomalies and choroidal neovascularization [1].

In conclusion, PIK3C2B plays crucial roles in lipid signalling and related biological processes. Research using gene knockout or conditional knockout mouse models has revealed its significance in diseases like myotubular myopathy, focal epilepsy, and age-related macular degeneration, providing potential therapeutic targets for these conditions.