AGL, also known as amylo-α-1,6-glucosidase,4-α-glucanotransferase, is an enzyme mainly responsible for glycogen debranching. Mutations in the AGL gene can lead to glycogen storage disease type III (GSDIII), indicating its crucial role in glycogen metabolism [1,2,4].

Germline Agl knockout (Agl-/-) and urothelium-specific conditional Agl knockout (Aglcko) mouse models have been developed. Agl-/-mice exposed to N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) had a higher bladder cancer (BC) incidence compared with wild-type mice. Similarly, Aglcko mice had a higher BC incidence than control (Aglfl/fl) mice. RNA sequencing of tumors from Agl-/-mice identified 19 differentially expressed genes. An 'Agl Loss' gene signature was developed and could stratify normal and tumor samples in BC patient datasets. These suggest that AGL loss promotes carcinogenesis [3]. Also, in bladder cancer, low AGL expression was found to enhance tumor growth by increasing hyaluronic acid synthase 2 (HAS2)-driven hyaluronic acid (HA) synthesis [5].

In conclusion, AGL is essential for glycogen debranching and normal glycogen metabolism. Mouse models with Agl knockout or conditional knockout have revealed its role in promoting bladder carcinogenesis, providing a basis for evaluating Agl expression levels in populations at risk of BC. This research helps in understanding the biological functions of AGL and its implications in disease, especially in bladder cancer.