Shelled pteropods play key roles in the global carbon cycle and foodwebs of various ecosystems. Their thin external shell is extremely sensitive to changes in pH and shell dissolution has already been observed in areas where aragonite saturation state is ~ 1. A decline in pteropod abundance has the potential to disrupt trophic networks and directly impact commercial fisheries. Therefore it is crucial to understand how pteropods will be affected by global environmental change, particularly ocean acidification. In the present study, physiological and molecular approaches were used to investigate the response of the Mediterranean pteropod, Heliconoides inflatus, to pH values projected for 2100 under a moderate emissions trajectory (RCP6.0). Pteropods were subjected to pHT 7.9 for 3d and gene expression levels, calcification and respiration rates measured relative to pHT 8.1 controls. Gross calcification decreased markedly under low pH conditions, while genes potentially involved in calcification were up-regulated, reflecting the inability of pteropods to maintain calcification rates. Gene expression data imply that under low pH conditions both metabolic processes and protein synthesis may be compromised, while genes involved in acid-base regulation were up-regulated. A large number of genes related to nervous system structure and function were also up-regulated in the low pH treatment, including a GABAA receptor subunit. This is particularly interesting because GABAA receptor disturbances, leading to altered behaviour, have been documented in several other marine animals after exposure to elevated CO2. The up-regulation of many genes involved in nervous system function suggests that, in addition to its impacts on other aspects of biology, exposure to low pH could have major effects on pteropod behavior. This study not only illustrates the utility of combining physiological and molecular approaches, but also highlights the desirability of including behavioural analyses in studies aimed at understanding the impacts of low pH on marine animals. Overall design: Six biological samples were sequenced, 3 replicates for the control condition and 3 replicates for the treatment. All samples were sequenced twice except the replicate treatment #3.