A study by Dongiovanni et al. reported that non-synonymous SNPs in ectoenzyme nucleotide pyrophosphate phosphodiesterase 1 (ENPP1 or PC1) (rs1044498, K121Q) and insulin receptor substrate-1 (IRS1) (rs1801278, Q972R), are associated with insulin resistance, through impairment of insulin receptor-mediated pathways, such as reduced AKT activation, and promote fibrosis in NAFLD patients [32]. This evidence concerns the gene ENPP1 and metabolic dysfunction-associated steatotic liver disease.