Ppargc1a, also known as peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α), is a transcription coactivator that plays a central role in regulating cellular energy metabolism [4]. It is involved in pathways such as mitochondrial biogenesis, controlling the remodeling of muscle tissue fiber-type composition, and regulating both carbohydrate and lipid metabolism [4]. Ppargc1a is highly likely to be associated with disorders like obesity, diabetes, and cardiomyopathy [4]. Genetic models, especially KO/CKO mouse models, can be valuable for studying its functions.

In hepatocellular carcinoma (HCC), low expression of Ppargc1a is associated with poor prognosis, and it impairs the progression and sensitivity of HCC to lenvatinib. Mechanistically, it represses BAMBI via inhibiting WNT/β -catenin signaling, and BAMBI in turn regulates ACSL5 through TGF-β/SMAD signaling. The Ppargc1a/BAMBI/ACSL5 axis is hypoxia-responsive [1]. In oral cancer cells, Ppargc1a activates mitochondrial biogenesis during CLU-induced mitophagy to maintain the mitochondrial pool, and its inhibition can lead to mitophagy-associated cell death [2]. Regarding metabolic diseases, the Gly482Ser polymorphism of Ppargc1a may be related to thrifty metabolism in the Pacific population, with inconsistent results in different ethnic groups [3].

In conclusion, Ppargc1a is a key regulator of energy metabolism, participating in mitochondrial biogenesis, muscle fiber-type regulation, and metabolism-related pathways. Model-based research, especially through KO/CKO mouse models, has revealed its roles in diseases such as HCC, oral cancer, and metabolic diseases, helping to understand its biological functions and the underlying disease mechanisms.