Wac, short for WW domain-containing coiled-coil adaptor, is primarily associated with transcriptional regulation, autophagy, and also plays a role in facilitating mitotic entry [2,3]. It has been implicated in several biological processes including osteogenic differentiation of mesenchymal stem cells (MSCs) and the progression of mitosis. In the context of disease, it is relevant to conditions like osteoporosis and potentially in the regulation of ferroptosis in renal allograft ischemia-reperfusion injury [2,1].

In osteoporosis, the levels of Wac are diminished in both patients and mouse models. Knockout of Wac would likely disrupt its function of facilitating MSC osteogenesis and enhancing new bone formation, as Wac promotes MSC osteogenesis by protecting PINK1 from ubiquitination-dependent degradation [2].

In the study of renal allograft ischemia-reperfusion injury, although the direct role of Wac gene knockout was not mentioned, inhibition of small extracellular vesicles (sEVs) biogenesis (which deliver lncRNA WAC-AS1) and knockout of lncRNA WAC-AS1 in IRI-sEVs diminished the "wave of ferroptosis" propagation, suggesting an indirect link of Wac-related pathways in this condition [1].

In summary, Wac plays essential roles in osteogenesis and potentially in regulating ferroptosis-related processes in renal allograft injury. The study of Wac through models such as gene knockout in osteoporosis mouse models has provided insights into its role in bone-related diseases. These findings contribute to our understanding of the underlying mechanisms of these diseases and may offer potential therapeutic targets [1,2].