SOX5, short for SRY-box transcription factor 5, is a transcription factor containing a High Mobility Group (HMG) DNA-Binding domain. It plays crucial roles in regulating cell fate and differentiation in processes like neurogenesis and chondrogenesis [2,3,9]. In neurogenesis, it is involved in the development of the nervous system, and in chondrogenesis, it is important for cartilage development [3,7].

In a genome-wide CRISPR activation screening, SOX5 was identified as a driver of rejuvenation in senescent cells. Overexpressing SOX5 reset the transcription network for geroprotective genes like HMGB2, promoting rejuvenation both in vitro and in vivo [1].

In the context of Lamb-Shaffer syndrome, caused by SOX5 haploinsufficiency, various genetic alterations in SOX5 lead to variable degrees of intellectual disability, language delay, and other clinical features [2,3,4].

In Kaposi's sarcoma, SOX5 acts as a suppressor factor, with its overexpression inhibiting cell proliferation and promoting apoptosis [5].

In bladder cancer, SOX5 promotes cell growth and migration through the SOX5/DNMT1/p21 pathway [6]. In breast cancer, it promotes proliferation and invasion by transactivating EZH2 [8].

In conclusion, SOX5 is essential in multiple biological processes and is associated with various disease conditions. Studies on SOX5, especially through genetic models in the context of these diseases, have provided insights into its role in cell fate determination, development, and disease pathogenesis, potentially offering new therapeutic targets for age-related pathologies, Lamb-Shaffer syndrome, and certain cancers.