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Even though <jats:italic>Nemp1<\/jats:italic> knockout (KO) mice are overtly normal, they display a pronounced splenomegaly. This phenotype and recent reports describing a requirement for NE openings during erythroblasts terminal maturation led us to examine a potential role for Nemp1 in erythropoiesis. Here, we report that <jats:italic>Nemp1<\/jats:italic> KO mice show peripheral blood defects, anemia in neonates, ineffective erythropoiesis, splenomegaly, and stress erythropoiesis. The erythroid lineage of <jats:italic>Nemp1<\/jats:italic> KO mice is overrepresented until the pronounced apoptosis of polychromatophilic erythroblasts. We show that NEMP1 localizes to the NE of erythroblasts and their progenitors. Mechanistically, we discovered that NEMP1 accumulates into aggregates that localize near or at the edge of NE openings and <jats:italic>Nemp1<\/jats:italic> deficiency leads to a marked decrease of both NE openings and ensuing enucleation. Together, our results for the first time demonstrate that NEMP1 is essential for NE openings and erythropoietic maturation in vivo and provide the first mouse model of defective erythropoiesis directly linked to the loss of an INM protein.<\/jats:p>","DOI":"10.1371\/journal.pbio.3001811","type":"journal-article","created":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T17:55:23Z","timestamp":1665424523000},"page":"e3001811","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["The inner nuclear membrane protein NEMP1 supports nuclear envelope openings and enucleation of 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