M6pr, also known as the mannose-6-phosphate receptor, exists in two forms: cation-independent (CI-M6PR) and cation-dependent (CD-M6PR). Its essential function is to coordinate the targeting of lysosomal enzymes to lysosomes, playing a crucial role in the autophagic-lysosomal reformation pathway [1]. This process is vital for maintaining normal lysosomal function, which is associated with various biological processes such as intracellular protein degradation and cellular homeostasis.

Mutations in CLN3, the Batten disease-related gene, lead to mis-trafficking of CI-M6PR, mis-sorting of lysosomal enzymes, and defective autophagic lysosomal reformation [1]. In esophageal cancer, exosomal M6PR from serglycin-overexpressing cells promotes tumor angiogenesis, and its high serum level is associated with poor overall survival [2]. For influenza A virus, M6PR is a crucial host factor, interacting with the HA2 subunit of the virus to facilitate the fusion of viral and endosomal membranes [3]. In the case of respiratory syncytial virus (RSV), Gimap5 promotes RSV degradation through interaction with M6PR [4].

In conclusion, M6pr is essential for lysosomal enzyme targeting and autophagic-lysosomal reformation. Its malfunction is associated with neurodegenerative diseases like Batten disease, and it also plays roles in cancer progression and viral infections. The study of M6pr using genetic models, such as those related to CLN3 mutations, helps in understanding its functions in disease-related biological processes, providing potential targets for therapeutic interventions.