Enho, also known as the energy homeostasis-associated gene, codes for the secreted protein adropin. Adropin is involved in multiple physiological and pathological processes. It plays a crucial role in energy homeostasis, adiposity, glycemia, and insulin resistance [3]. Additionally, it has been implicated in processes like angiogenesis, apoptosis, and endothelial-to-mesenchymal transition (EndMT), with potential links to the TGF-β/Smad2/3 signaling pathway [1,2,5,6].

In ApoE-/-/Enho-/-mice, an intraperitoneal injection of adropin inhibited the progression of high-fat diet-induced aortic atherosclerosis by regulating EndMT [1]. In systemic sclerosis, adropin/Enho was down-regulated in skin, and restoration of adropin signaling inhibited fibroblast activation and fibrotic tissue remodeling [2]. In MPO-ANCA associated lung injury, Enho mutations led to low adropin levels, causing pulmonary alveolar hemorrhage in adropin knockout mice, along with reduced eNOS and Akt1 phosphorylation and loss of Treg cells [4].

In conclusion, Enho, through its encoded protein adropin, is involved in energy homeostasis and plays important roles in various disease conditions such as atherosclerosis, systemic sclerosis, and MPO-ANCA associated lung injury. Gene knockout mouse models have been instrumental in revealing these functions, providing insights into the molecular mechanisms underlying these diseases and potentially guiding future therapeutic strategies.