“…The lipid surface area would still be significantly greater than that of the transporter protein.” Counter: The surface area per se is not the question. What matters is the extent to which the presence of high amounts of protein in a cell membrane (Dupuy and Engelman, 2008), often binding specific lipids (Laganowsky et al, 2014) (including cholesterol; Song et al, 2014) and certainly altering their organization (Mitra et al, 2004; Engelman, 2005; Mclaughlin and Murray, 2005; Beswick et al, 2011; Coskun and Simons, 2011; Kusumi et al, 2011; Lee, 2011a,b; Domański et al, 2012; KoldsØ and Sansom, 2012; Magalon et al, 2012; Mueller et al, 2012; Smith, 2012; Goose and Sansom, 2013; Javanainen et al, 2013; Van Der Cruijsen et al, 2013) (and vice versa ; Li et al, 2012; Denning and Beckstein, 2013), alters any ability of drug molecules to cross via the lipoidal bilayer part of the membranes in which these proteins exist. This means that any direct change of lipids will also have the potential likelihood of affecting transporters, so is not of itself a discriminating experiment if transporter activities are not measured.…”