Hnrnpa1, short for Heterogeneous nuclear ribonucleoprotein A1, is an RNA-binding protein involved in multiple biological processes. It participates in mRNA processing, such as RNA splicing, and is associated with pathways related to lipid and glucose metabolism, cell growth, and neurodegeneration [1-4]. Its role in various biological functions makes it crucial for maintaining normal cellular and organismal homeostasis, and genetic models like knockout (KO) mouse models are valuable for studying its functions.

In adipocyte-specific Hnrnpa1 knockout (KO) mice, the depletion of Hnrnpa1 in adipocytes exacerbates obesity-induced metabolic dysfunction. It leads to increased macrophage infiltration and upregulation of pro-inflammatory and fibrosis genes in white adipose tissue (WAT), ultimately worsening insulin sensitivity, glucose tolerance, and hepatic steatosis. Mechanistically, Hnrnpa1 interacts with Ccl2 and regulates its mRNA stability [1]. In addition, mutations in Hnrnpa1 in families can cause inherited degeneration affecting muscle, brain, motor neuron, and bone, and in some cases, familial amyotrophic lateral sclerosis. The disease-causing mutations accelerate the formation of self-seeding fibrils and promote the abnormal incorporation of Hnrnpa1 into stress granules, recapitulating human pathology [2].

In conclusion, Hnrnpa1 is essential for mRNA processing and plays a key role in regulating lipid and glucose metabolism, as well as in neurodegenerative processes. The study of Hnrnpa1 KO mouse models has provided insights into its role in obesity-related metabolic dysfunction and neurodegenerative diseases, which may contribute to the development of new therapeutic strategies for these conditions.