Novel α,ω-functionalized amphiphilic lipopolymers are prepared that are composed of a proximal lipid moiety and a hydrophilic poly(2-oxazoline)-based (POx) polymer chain. The synthesis begins from bifunctional lipoinitiators, which are asymmetrically protected as tert.butyldiphenylsilyl (TBDPS) ethers, followed by cationic living ring-opening polymerization of 2-oxazolines in a one-pot multistep reaction. This results in polymers with defined terminal end groups and narrow molar mass distributions. All protective groups involved can be readily cleaved in a single step reaction keeping the structure of the polymer intact, giving access to (lipo)polymers with a variety of defined identical or chemical orthogonal α,ω- functionalities. The synthetic strategy is a versatile tool for the preparation of defined polymer-drug or polymer-protein conjugates or asymmetric functionalized model lipid membranes for the quantitative study of membrane-associated phenomena such as transmembrane transport and cell adhesion/recognition.(Figure Presented)