SH3GLB1, also known as Bax-interacting factor 1 (Bif-1) and Endophilin B1, is a protein-coding gene involved in multiple cellular processes. It participates in autophagy and apoptosis pathways, which are essential for maintaining cellular homeostasis and normal development. SH3GLB1 is also associated with mitochondrial metabolism, and its regulation is crucial for normal cell function [2,3,4]. Genetic models, such as gene knockout mouse models, have been instrumental in understanding its function.

In Bif-1 -/- mice, an increase in trabecular bone volume and number was observed, along with an acceleration of osteoclastogenesis induced by receptor activator of nuclear factor-κB ligand (RANKL) without affecting downstream signals. Unexpectedly, both bone formation rate and osteoblast surface also increased, suggesting Bif-1 regulates bone homeostasis by controlling the differentiation and function of both osteoclasts and osteoblasts [3]. In glioblastoma, high SH3GLB1 gene expression was associated with higher disease grading and worse survival. Downregulation of SH3GLB1 retained temozolomide susceptibility, and inhibition of SH3GLB1 in resistant cells alleviated temozolomide-enhanced mitochondrial metabolic function, indicating SH3GLB1 promotes temozolomide resistance via autophagy to alter mitochondrial function [1].

In summary, SH3GLB1 plays a vital role in regulating autophagy, apoptosis, and mitochondrial metabolism. Research using gene knockout mouse models has revealed its significance in diseases like glioblastoma and in maintaining bone homeostasis. Understanding SH3GLB1's functions provides insights into disease mechanisms and may contribute to developing new therapeutic strategies for related diseases.