Caspase-recruitment domain 9 (CARD9), an adaptor protein, is expressed in many cells, especially immune cells. It's crucial for the innate and adaptive immune systems, transducing signals from pattern recognition receptors (PRRs) and interacting with pathways like NF-κB and MAPK. CARD9-mediated signaling regulates inflammatory responses, oxidative stress, and cytokine/chemokine production, playing a significant role in maintaining immune homeostasis [1,2].

In mice, Card9 knockout (KO) has revealed its functions in various disease conditions. In myocardial infarction, Card9 KO in macrophages improved left ventricular function, reduced infarct scar size, suppressed cardiomyocyte apoptosis, and attenuated matrix metalloproteinase expression, likely through regulating lipocalin 2 (Lcn2) expression [3]. In colitis, CARD9 in neutrophils protected from disease as Card9 deletion led to mitochondrial dysfunction, increased apoptosis of neutrophils, and enhanced susceptibility to intestinal inflammation [5]. Also, in ankylosing spondylitis, experiments in SKG mice showed Card9 was essential for Th17 cell induction and disease onset, functioning downstream of Dectin-1 and controlling neutrophil function [4].

In conclusion, CARD9 is a key regulator in the immune system, with its functions revealed through KO mouse models. These models have demonstrated its importance in cardiovascular diseases like myocardial infarction, inflammatory bowel diseases such as colitis, and autoimmune diseases like ankylosing spondylitis, providing insights into disease mechanisms and potential therapeutic targets.