Abstract: The invention relates generally to compounds which are allosteric modulators (e.g., negative and positive allosteric modulators, allosteric agonists, and ago-allosteric modulators) of the G protein coupled receptor apelin, also known as the APJ receptor. The APJ receptor compounds are derived from the intracellular loops and domains of the the APJ receptor. The invention also relates to the use of these APJ receptor compounds and pharmaceutical compositions comprising the APJ receptor compounds in the treatment of diseases and conditions associated with APJ receptor modulation, such as heart diseases (e.g., hypertension and tension and heart failure, such as congestive heart failure), cancer, diabetes, stem cell trafficking, fluid homeostasis, cell proliferation, immune function, obesity, metastatic disease, and HIV infection.