BIN1, also known as bridging integrator 1 or amphiphysin-2, belongs to the BIN1/amphiphysin/RVS167 (BAR) superfamily. It plays crucial roles in multiple biological processes such as membrane dynamics, including endocytosis, membrane cycling, and cytoskeletal regulation [2,4,6]. It is also involved in DNA repair deficiency, cell-cycle arrest, and apoptosis [2]. The gene is associated with various pathways like those related to inflammation, neurodegeneration, and cardiac function [1,3,7].

In microglia, Bin1 knockdown by siRNA in vitro and Cre-lox mediated conditional deletion in vivo demonstrated that BIN1 regulates pro-inflammatory and neurodegeneration-related activation. Loss of Bin1 impaired the ability of microglia to mount type 1 interferon responses, especially the up-regulation of Ifitm3, a critical type 1 immune response gene [1].

In mouse hippocampal neurons, Bin1 knockdown via RNAi reduced dendritic arbor size, and autophagy inhibition mitigated this effect. The increase in ULK3-dependent autophagic flux was observed in BIN1 deficiency [5].

In the heart, age-associated overexpression of BIN1 led to cardiac dysfunction, and BIN1 knockdown using an adeno-associated virus serotype 9 packaged shRNA-mBIN1 restored cardiac systolic function in old mice [8].

In conclusion, BIN1 is essential in regulating membrane-related functions, inflammation, and cell-cycle-related processes. Gene knockout and conditional knockout mouse models have revealed its significant roles in neurodegenerative diseases like Alzheimer's, cardiac function, and microglial-mediated inflammation, providing insights into potential therapeutic targets for these disease areas.