The sarcoplasmic-endoplasmic reticulum Ca(2+)-ATPase (SERCA) is the likely molecular target for the acute toxicity of the brominated flame retardant hexabromocyclododecane (HBCD).

•HBCD is the most potent BFR tested to inhibit SERCA Ca2+ pumps.•HBCD is the most potent at inducing death of SH-SY5Y cells.•For a range of BFRs there is a correlation between cell death & SERCA inhibition.•HBCD inhibits ATP binding and the E2 to E1 transition of SERCA.