Annexins are a family of soluble proteins that bind to acidic phospholipids such 
as phosphatidylserine in a calcium-dependent manner. The archetypical member of 
the annexin family is annexin A5. For many years, its function remained unknown 
despite the availability of a high-resolution structure. This, combined with the 
observations of specific ion conductance in annexin-bound membranes, fueled 
speculations about the possible membrane-spanning forms of annexins that 
functioned as ion channels. The channel hypothesis remained controversial and 
did not gather sufficient evidence to become accepted. Yet, it continues to draw 
attention as a framework for interpreting indirect (e.g., biochemical) data. The 
goal of the mini-review is to examine the data on annexin-lipid interactions 
from the last ~30 years from the point of view of the controversy between the 
two lines of inquiry: the well-characterized peripheral assembly of the annexins 
at membranes vs. their putative transmembrane insertion. In particular, the 
potential role of lipid rearrangements induced by annexin binding is 
highlighted.