Sh3bgrl, also known as SH3 domain binding glutamate-rich protein-like, is an adaptor protein. It is involved in multiple biological processes. In cancer-related pathways, it impacts autophagy, cell cycle regulation, and signaling pathways such as Src-related ERK and AKT, HER2-related signaling, and AKT, NF-κB, and WNT pathways. In female reproduction, it is crucial for normal ovarian function [6].

In breast cancer, Sh3bgrl upregulation enhances chemoresistance to doxorubicin through promoting PIK3C3 translation and ATG12 stability, driving autophagy-mediated protection [1]. It also promotes breast cancer metastasis by downregulating PFN1 via translational STUB1 upregulation [3].

In liver cancer, Sh3bgrl overexpression inhibits cell proliferation and tumorigenesis by enhancing ATG5-dependent autophagy [2].

In acute myeloid leukemia, it is down-regulated, and its down-regulation promotes cell cycle progression and anti-apoptotic ability, while ectopic expression blocks cell cycle and sensitizes cells to drugs [4].

In lung cancer, it is down-regulated in cancer tissues and CSCs, and overexpression suppresses CSCs self-renewal [5].

In zebrafish, loss of Sh3bgrl leads to ovarian fibrosis and female spawning inability due to upregulation of ECM-associated genes [6].

In conclusion, Sh3bgrl plays diverse and significant roles in cancer development and female reproduction. Studies, including those using loss-of-function models, have revealed its functions in promoting or suppressing tumorigenesis in different cancers and its importance in maintaining normal ovarian function, providing potential diagnostic and therapeutic targets for related diseases.