Ybx1, also known as Y-box binding protein 1, is an RNA-binding protein and splicing factor. It is involved in various biological processes by regulating RNA transcripts and gene expression. It has been associated with pathways such as angiogenesis-dependent bone formation, and plays a role in the development of multiple diseases, highlighting its overall biological importance. Genetic models, especially gene knockout (KO) or conditional knockout (CKO) mouse models, are valuable for studying its functions [1,3].

In endothelial cell-specific Ybx1 knockout mice, CD31-high, endomucin-high (CD31hiEMCNhi) endothelium morphology was impaired, leading to low bone mass, indicating Ybx1's role in angiogenesis-dependent osteogenesis [1]. In myeloid leukemia cells, deletion of Ybx1 induced apoptosis, promoted differentiation, and reduced proliferation, suggesting its essential role in maintaining myeloid leukemia cell survival [2]. In bone marrow stromal cells (BMSCs), Ybx1 deficiency led to mis-splicing in genes related to BMSC osteogenic differentiation and senescence, accelerating bone loss in mice [3]. CircNEIL3 inhibited tumor metastasis by promoting Nedd4L-mediated proteasomal degradation of YBX1 in various cancer types [4].

In conclusion, Ybx1 is crucial for multiple biological functions including angiogenesis-dependent bone formation, maintenance of myeloid leukemia cell survival, and regulation of BMSC fate. KO/CKO mouse models have been instrumental in revealing its roles in osteoporosis-related bone loss and myeloid leukemia, providing insights into potential therapeutic strategies for these disease areas.