Mapkapk3, short for mitogen-activated protein kinase-activated protein kinase 3, is a serine/threonine protein kinase. It is a key component of the p38 mitogen-activated protein kinase (MAPK) signaling pathway, which is activated by various stress stimuli such as heat, osmotic shock, and pro-inflammatory cytokines. Mapkapk3 is involved in cellular responses, gene regulation, and is essential for normal cell function and stress adaptation [2].

In a study of a large family with a retinal disease, a heterozygous c.518T>C (p.Leu173Pro) mutation in Mapkapk3 was identified. The mutated protein was predicted to be non-functional, and its mislocalization in the cytoplasm led to cytoskeleton alteration and cytodieresis inhibition. In Mapkapk3-/-mice, Bruch's membrane was irregular, with abnormal thickened and thinned portions, suggesting a role for Mapkapk3 in retinal physiology and Bruch's membrane/RPE pathophysiology [2]. Another study showed that Mapkapk3 can activate starvation-induced autophagy by phosphorylating Beclin 1 at serine 90, and this phosphorylation is blocked by BCL2 [1].

In conclusion, Mapkapk3 plays a crucial role in stress-related cellular responses, autophagy regulation, and retinal physiology. The gene knockout mouse models have provided valuable insights into its role in retinal diseases, highlighting its potential as a target for further research in understanding and treating diseases related to Bruch's membrane and retinal pigment epithelium alterations [1,2].