Animal models to study MASLD progression and evaluate key disease-associated genetic variants such as the PNPLA3 GG polymorphism have been characterized with various metrics demonstrating increased steatosis, inflammation, fibrogenesis, oxidative stress, and insulin resistance yet do not fully recapitulate the complex and heterogeneous progression of the human disease (Flessa et al., 2022; Hebbard and George, 2011; Jahn et al., 2019; Takahashi et al., 2012; Van Herck et al., 2017; Zhong et al., 2024). This evidence concerns the gene PNPLA3 and steatosis.