Tnip1, also known as tumour necrosis factor α -induced protein 3 -interacting protein 1 or ABIN1, is a key regulator with diverse functions. It acts as a negative regulator of mitophagy, inhibiting the process at the early steps of autophagosome biogenesis through interaction with LC3/GABARAP and TAX1BP1, and its phosphorylation-regulated association with FIP200 allows it to compete with autophagy receptors [1]. It also plays a role in inflammatory signaling regulation, being a potential factor in multiple autoimmune diseases and regulating Toll-like receptor signaling [3].

In autoimmune diseases, a heterozygous TNIP1Q333P variant in humans and the orthologous Q346P variant in mice led to the development of autoantibodies, salivary gland inflammation, and other phenotypes. The variant increased interferon-β, impaired recruitment of MyD88 and IRAK1 to autophagosomes, and affected TNIP1 localization to damaged mitochondria and mitophagosome formation [4]. In glioma, high levels of TNIP1 and TNF-α/NF-κB were found. Loss of TNIP1 disrupted the A20 complex for IκB degradation and NF-κB nucleus translocation, erasing TNFα-induced glioma cell proliferation [5]. In diabetes-induced vascular endothelial dysfunction, FTO regulated TNIP1 expression by erasing its m6A methylation, and TNIP1 depletion activated NF-κB and other inflammatory factors, aggravating endothelial impairments [2].

In conclusion, Tnip1 is crucial in regulating selective autophagy, especially mitophagy, and inflammatory signaling. Gene-knockout models, like the mouse models with TNIP1 variants, have been instrumental in revealing its role in autoimmune diseases, glioma, and diabetic vascular complications, providing insights into disease mechanisms and potential therapeutic targets.