The sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) is a P-type ATPase embedded in the sarco-plasmic reticulum. For each enzymatic cycle, SERCA transports 2 Ca2+ ions per ATP hydrolyzed in ex-change for 2 to 3 H+ ions. SERCA is responsible for approximately 70% of Ca2+ transport and plays a central role in muscle relaxation. SERCA's function is regulated by endogenous regulins, single-pass membrane proteins that bind the ATPase within the membrane. While most of the regulins, such as phospholamban and sarcolipin, inhibit SERCA's activity, a newly discovered protein DWarf Open Reading Frame (DWORF) has a unique activating effect. DWORF is a 3.8 kDa bitopic membrane protein expressed in cardiac muscle. In this work, we determine the structure, topology, and per-residue lipid interactions of DWORF in lipid bilayers using a combination of high-resolution oriented sample solid-state NMR (OS-ssNMR) spectroscopy and refinement by replica-averaged orientationally-restrained molecular dynamics (RAOR-MD). We found that DWORF's structural topology consists of a dynamic N-terminal domain, an amphipathic juxtamembrane helix that crosses the lipid groups at an angle of 64 degrees and a transmembrane (TM) C-terminal helix with an angle of 32 degrees. A kink induced by Pro15, unique to DWORF, separated the two helical domains. A single Pro15Ala mutant significantly decreases the kink and eliminates DWORF's activating effect on SERCA. Overall, our findings directly link DWORF's structural topology to its unique activating effect on SERCA.