WHAMM, short for WAS Protein Homolog Associated with Actin, Golgi Membranes, and Microtubules, is an actin nucleation promoting factor (NPF) belonging to the Wiskott-Aldrich syndrome protein (WASP) family. It associates with membranes and microtubules and is involved in important cellular processes such as autophagic lysosome reformation (ALR), autophagosome membrane remodeling, and kidney nutrient reabsorption [1,2,5]. It also plays a role in oocyte maturation and spindle formation in mammalian cells [3].

In male WHAMM knockout mice, there is impaired kidney reabsorption, as evidenced by elevated excretion of albumin, glucose, phosphate, and amino acids, along with structural abnormalities in the kidney proximal tubule. In kidney tissue, loss of WHAMM leads to accumulation of lipidated autophagosomal membrane protein LC3, indicating autophagy alteration. In cells, WHAMM and its binding partner Arp2/3 complex control autophagic membrane closure and cargo receptor recruitment [2,4]. In maturing mouse oocytes, knockdown of WHAMM impairs spindle formation, spindle actin polymerization, chromosome alignment, and can cause chromosomal aneuploidy and abnormal, asymmetric division [3].

In conclusion, WHAMM is essential for multiple biological functions, especially in processes related to autophagy and cytoskeletal regulation. The use of WHAMM knockout mouse models has revealed its significance in kidney function and oocyte maturation, which may have implications for understanding related diseases such as kidney disorders and potential fertility-related issues.