NPM1 is associated with nucleolar ribonucleoprotein structures and bind single-stranded nucleic acids. It may be involved in the assembly and/or transport of ribosome. Its regulation through SUMOylation (by SENP3 and SENP5) is another facet of the proteins's regulation and cellular functions. It is located in nucleolus, but it can be translocated to the nucleoplasm in case of serum starvation or treatment with anticancer drugs. The protein is phosphorylated.

Chromosomal aberrations involving NPM1 were found in patients with non-Hodgkin lymphoma, acute promyelocytic leukemia, myelodysplastic syndrome, and acute myelogenous leukemia.It has been found in the cytoplasm in patients with primary acute myelogenous leukemia.