Background: Transcription factors are critical in regulating lens development. The AP‐2 family of transcription factors functions in differentiation, cell growth and apoptosis, and in lens and eye development. AP‐2α, in particular, is important in early lens development, and when conditionally deleted at the placode stage defective separation of the lens vesicle from the surface ectoderm results. AP‐2α's role during later stages of lens development is unknown. To address this, the MLR10‐Cre transgene was used to delete AP‐2α from the lens epithelium beginning at embryonic day (E) 10.5. Results: The loss of AP‐2α after lens vesicle separation resulted in morphological defects beginning at E18.5. By P4, a small highly vacuolated lens with a multilayered epithelium was evident in the MLR10‐AP‐2α mutants. Epithelial cells appeared elongated and expressed fiber cell specific βB1 and γ‐crystallins. Epithelial cell polarity and lens cell adhesion was disrupted and accompanied by the misexpression of ZO‐1, N‐Cadherin, and β‐catenin. Cell death was observed in the mutant lens epithelium between postnatal day (P) 14 and P30, and correlated with altered arrangements of cells within the epithelium. Conclusions: Our findings demonstrate that AP‐2α continues to be required after lens vesicle separation to maintain a normal lens epithelial cell phenotype and overall lens integrity and to ensure correct fiber cell differentiation. Developmental Dynamics 243:1298–1309, 2014. © 2014 Wiley Periodicals, Inc.