CSF3R encodes the granulocyte colony-stimulating factor (G-CSF) receptor, a cytokine receptor essential for neutrophil maturation, proliferation, and survival 1. The receptor mediates G-CSF signaling through JAK-STAT pathway activation, promoting granulocytic differentiation and lineage commitment 2. Beyond hematopoiesis, CSF3R participates in cell adhesion and recognition events at the cell surface. CSF3R mutations drive chr1 neutrophilic leukemia (CNL), a myeloproliferative neoplasm with the T618I variant present in >80% of cases 3. This activating mutation causes constitutive JAK-STAT signaling, leading to uncontrolled neutrophil proliferation 2. CSF3R mutations also contribute to malignant progression in severe congenital neutropenia patients 1 and can accumulate during clonal evolution from myelodysplastic syndromes to secondary CNL 4. Germline CSF3R mutations cause autosomal recessive severe congenital neutropenia type 7, characterized by impaired neutrophil maturation and life-threatening infections 1. Clinically, CSF3R-mutated diseases show poor prognosis with 15-31 month median survival in CNL 3. JAK inhibitor ruxolitinib demonstrates modest efficacy (32-35% response rate) in CSF3R-mutated cases 2. Beyond hematologic malignancies, CSF3R signaling in non-hematopoietic tissues promotes tumor microenvironment remodeling in metastatic breast cancer 5, and CSF3R activation drives hepatocellular carcinoma progression through JAK2/STAT3 feedback loops 6.