Aiolos protein is a transcription factor that belongs to the Ikaros family of zinc finger proteins, encoded by the Ikzf3 gene. It plays a crucial role in the development and function of various immune cells, regulating gene expression directly by promoting the transcription of specific genes and indirectly by silencing gene expression through chromatin remodeling. Aiolos protein is particularly important in the context of tissue-resident type 2 innate immune cells. Studies have shown that Aiolos can shape the transcriptome profile and chromatin landscape, which is essential for the positioning and function of tissue-resident eosinophils and group 2 innate lymphoid cells (ILC2s). Aiolos is specifically expressed in intestinal ILC2s of mice and human colon ILC2s and is associated with tissue residency in the gut. The expression of Aiolos protein in eosinophils and ILC2s is crucial for their tissue positioning and functionality. For instance, Aiolos regulates the expression of CCR3 in eosinophils and the expression of 371 genes associated with ERK/MAPK signaling and chemotaxis. Additionally, Aiolos plays a role in the positioning of eosinophils in the gut and lungs. Furthermore, the expression of Aiolos protein in lung cancer is associated with enhanced proliferation, migration, and invasion capabilities of lung cancer cells. Studies suggest that OTUB1 interacts with Aiolos protein, leading to reduced ubiquitination and increased protein stability of Aiolos, potentially affecting biological functions related to Aiolos, including cell migration and invasion.