The a 1A-adrenoceptor is therapeutically exploited because of its prevalence in the lower urinary tract. The pharmacology shown by this lower urinary tract a 1A-adrenoceptor is different from that shown by other a 1A-adrenoceptors, which has led to it being subclassified as an a 1L-adrenoceptor. Only in the last few years was it shown that this pharmacologically distinct a 1L- adrenoceptor is a product of the a 1A-adrenoceptor gene. In this issue of the BJP, Nishimune et al. review the literature on a 1L-adrenoceptor pharmacology and discuss the possible molecular mechanisms by which the a 1A-adrenoceptor gene is able to produce two pharmacologically distinct adrenoceptor subtypes. Based primarily from their own research using cell lines transfected with a 1A-adrenoceptors, they conclude that a protein that interacts with the receptor is the most plausible explanation. The challenge remains to identify any such interacting protein and show how it is able to change the pharmacology of the receptor for different ligands. ? 2011 The Author.