CYTH1 (cytohesin 1) is a guanine-nucleotide exchange factor (GEF) that activates ADP-ribosylation factors (ARF1, ARF5, and ARF6) by promoting GDP-to-GTP exchange 1. This activation is essential for regulating integrin-dependent adhesion, membrane trafficking, and epithelial cell polarization, particularly through ARF6-mediated signaling 12. CYTH1 controls homing and engraftment of hematopoietic stem and progenitor cells by mediating adhesion to stromal cells and integrin ligands like fibronectin and ICAM1 1. In neuronal development, CYTH1 participates in hippocampal pyramidal neuron migration and dendritogenesis through the ARL4C-CYTH1-ARF6 signaling cascade 2. Dysregulation of CYTH1 has significant pathological implications: overexpression in acute myeloid leukemia (AML) correlates with poor prognosis and enhanced leukemic cell adhesion and engraftment 3. The CYTH1 inhibitor SecinH3 suppresses AML progression and synergizes with venetoclax to overcome drug resistance 3. Additionally, CYTH1 is identified as a novel gene involved in Alzheimer's disease-related neuroinflammation through phospholipase D signaling 4, and its expression is altered in COPD pathogenesis via m6A RNA modification 5. Thus, CYTH1 represents a therapeutic target for hematologic malignancies and potential neurodegenerative diseases.