Secretory granules of neuroendocrine cells store and release peptide hormones and neuropeptides in response to various stimuli. Generation of granules from the Golgi complex involves the aggregation of cargo proteins and their sorting from non-regulated secretory molecules. Recent findings on knockout mice lacking individual granule constituents have challenged the hypothesis that an ‘essential’ protein for the assembly of these organelles exists, while studies on polypyrimidine tract-binding protein and ICA512/IA-2 have provided insight into the mechanisms for adjusting granule production in relation to stimulation and secretory activity.