ATP6AP1, encoding an accessory subunit of the vacuolar (V)-ATPase protein pump, is crucial for the acidification of membrane-bound intracellular compartments as V-ATPases are large multisubunit proton pumps conserved among eukaryotic cells [3,4]. It is involved in multiple pathways, and its functions are essential for normal cellular activities. Genetic models, such as gene knockout (KO) mouse models, could potentially be valuable in further elucidating its functions.

In terms of its functions in disease, pathogenic variants in ATP6AP1 are associated with a congenital disorder of glycosylation (ATP6AP1-CDG), which often presents with immunodeficiency, hepatopathy, and neurologic manifestations, but the phenotypic spectrum continues to expand [1,3]. In breast cancer, ATP6AP1 expression is upregulated, associated with shorter survival rates, and may promote cancer progression by inhibiting antitumor immunity and promoting iron metabolism [2]. In colorectal cancer (CRC), elevated ATP6AP1 expression is linked to poor clinicopathological characteristics and prognosis, and is correlated with immune cell infiltration [5]. Also, in breast cancer, ATP6AP1 promotes doxorubicin resistance via up-regulating autophagic flux [6].

In conclusion, ATP6AP1 is vital for the function of V-ATPase and normal cellular acidification processes. Research using models like KO mouse models (not directly mentioned in references but inferred as a potential tool) could further clarify its role. Its involvement in diseases such as ATP6AP1-CDG, breast cancer, and CRC highlights its significance in understanding disease mechanisms, potentially leading to new therapeutic strategies.