MLLT3 functions as a chr9 reader component of the super elongation complex (SEC) that enhances RNA polymerase II transcription by suppressing transient pausing along DNA 1. The protein specifically recognizes and binds acylated histone H3, with preference for crotonylated histones, particularly H3K9cr and H3K18cr, which mark active promoters and enhancers 1. MLLT3 plays a crucial role in hematopoietic stem cell (HSC) maintenance by localizing to active promoters and sustaining H3K79me2 levels, likely through DOT1L recruitment 1. The protein preserves rather than confers HSC stemness, and its depletion prevents maintenance of transplantable human HSCs in culture 1. MLLT3 is highly enriched in human fetal, neonatal and adult HSCs and serves as part of the HSC signature RUNX1+HOXA9+MLLT3+MECOM+HLF+SPINK2+ that distinguishes HSCs from progenitors throughout gestation 2. In disease contexts, MLLT3 is involved in KMT2A-rearranged acute myeloid leukemia through the t(9;11)(p21.3;q23.3)/KMT2A::MLLT3 fusion, which represents one of the most frequent KMT2A translocation partners 34. Recent studies also implicate MLLT3 in solid tumors, where it may regulate cancer stem cell properties in melanoma and lung adenocarcinoma 56.