Fstl3, also known as follistatin-like protein 3, is a cytokine that can regulate insulin sensitivity and counteract activin/myostatin signalling. It is involved in multiple biological processes, likely through its interactions with members of the transforming growth factor β (TGF-β) superfamily [6,8].

In various diseases, Fstl3 shows distinct roles. In type 2 diabetes mellitus patients with non-alcoholic fatty liver disease (NAFLD), increased NAFLD fibrosis risk is an independent risk factor for acute myocardial infarction (AMI), and serum Fstl3 partially mediates this association [1]. In colorectal cancer, Fstl3 promotes tumor immune evasion and attenuates response to anti-PD1 therapy by stabilizing c-Myc, while its cytoplasmic expression correlates with cancer progression, metastasis status, and prognosis [2,9]. In lung adenocarcinoma, Fstl3 expression is reduced, and it is associated with prognosis, disease progression, and immune cell infiltration [3]. In overweight or obese individuals, Fstl3 is highly expressed in adipose tissue and can suppress adipocyte inflammation, with serum levels potentially being a biomarker of visceral obesity and inflammation [4]. Also, Fstl3 is associated with atherosclerosis by inducing lipid accumulation and inflammatory response in macrophages [5], is upregulated in gastric cancer and may be involved in its progression [6], is a prognostic biomarker in pulmonary arterial hypertension [7], and is increased in renal dysfunction [8].

In conclusion, Fstl3 is a cytokine with diverse functions, playing important roles in metabolic, cardiovascular, and neoplastic diseases. Its study, potentially via gene knockout or conditional knockout mouse models, helps in understanding disease mechanisms and may offer new therapeutic targets for these diseases.