Emerging role of RNA modification reader YTHDF2 in hematopoiesis, immunity, and cancer.

N6-methyladenosine (m6A) RNA modification has emerged as a pivotal epitranscriptomic mark shaping RNA metabolism and cellular programs. Among the diverse m6A reader proteins, YTHDF2 has garnered significant attention as a key regulator of RNA stability. Recent studies highlight the multifaceted roles of YTHDF2 in orchestrating hematopoietic stem cell self-renewal and differentiation, fine-tuning immune cell development and function, and modulating tumor-immune interactions within the tumor microenvironment. YTHDF2 has also been shown to function as a reader for RNA 5-methylcytosine (m5C) modification. By linking m6A- and/or m5C-dependent RNA dynamics to hemato-immune homeostasis, YTHDF2 functions as a central epitranscriptomic integrator linking intrinsic genetic programs to developmental and environmental cues. Here, we summarize current advances in understanding YTHDF2-mediated RNA regulation across physiological and pathological contexts, discuss its potential as a therapeutic target in immune-related diseases and cancers, and highlight future directions in the field.