Rethinking holocrine secretion: functional logic in lipid-producing epithelia

Holocrine secretion is typically described as an exception among glandular strategies, distinguished by cell disintegration and release of cellular fragments rather than vesicular contents. Yet this description treats holocrine glands primarily as anatomical curiosities and leaves their underlying biological logic largely unexplored. Here, we propose that holocrine secretion can instead be understood as a differentiation program that couples lipid accumulation, terminal differentiation, and cell elimination. This design supports surface barrier function and points toward differentiation-based approaches for controlled epithelial cell removal.