MICL recognizes and controls neutrophil extracellular trap (NET) formation. MICL, an inhibitory C-type lectin receptor, directly binds DNA in NETs, regulating neutrophil activation. Loss or inhibition of MICL leads to uncontrolled NET formation via the ROS–PAD4 pathway and auto-inflammatory feedback loops. In rheumatoid arthritis, MICL autoantibodies inhibit MICL function, exacerbating disease. Similar autoantibodies are found in lupus and severe COVID-19, where NETs contribute to pathology. Conversely, dysregulated NET release is protective against Aspergillus fumigatus infection. MICL functions as a pattern recognition receptor (PRR) for NETs, preventing excessive inflammation and NET formation. In arthritis models, MICL deficiency increases neutrophil activation and NET formation, leading to exacerbated disease. Anti-MICL antibodies block receptor function, increasing disease severity. In patients with rheumatoid arthritis, anti-MICL autoantibodies correlate with disease severity. MICL also regulates NET formation during fungal infections, with MICL-deficient mice showing increased resistance to Aspergillus fumigatus. MICL is a key regulator of neutrophil activation and NET formation, preventing autoimmune disease and invasive infections. Targeting MICL with antibodies could treat fungal infections, while blocking MICL-receptor interactions may benefit NET-mediated inflammatory diseases. This study highlights MICL's role in maintaining immune homeostasis and its potential as a therapeutic target.MICL recognizes and controls neutrophil extracellular trap (NET) formation. MICL, an inhibitory C-type lectin receptor, directly binds DNA in NETs, regulating neutrophil activation. Loss or inhibition of MICL leads to uncontrolled NET formation via the ROS–PAD4 pathway and auto-inflammatory feedback loops. In rheumatoid arthritis, MICL autoantibodies inhibit MICL function, exacerbating disease. Similar autoantibodies are found in lupus and severe COVID-19, where NETs contribute to pathology. Conversely, dysregulated NET release is protective against Aspergillus fumigatus infection. MICL functions as a pattern recognition receptor (PRR) for NETs, preventing excessive inflammation and NET formation. In arthritis models, MICL deficiency increases neutrophil activation and NET formation, leading to exacerbated disease. Anti-MICL antibodies block receptor function, increasing disease severity. In patients with rheumatoid arthritis, anti-MICL autoantibodies correlate with disease severity. MICL also regulates NET formation during fungal infections, with MICL-deficient mice showing increased resistance to Aspergillus fumigatus. MICL is a key regulator of neutrophil activation and NET formation, preventing autoimmune disease and invasive infections. Targeting MICL with antibodies could treat fungal infections, while blocking MICL-receptor interactions may benefit NET-mediated inflammatory diseases. This study highlights MICL's role in maintaining immune homeostasis and its potential as a therapeutic target.