What does Psalm 53:4 mean?

David expresses shock that the wicked are ignorant of the evil they commit by persecuting God's people. They are so blind to their own evil that they do not "call on" God, either in the sense of obeying Him or even acknowledging His existence.

While it's true that some sin is extremely deliberate, some evils are done when a person confuses, fools, or distracts themselves and doesn't consciously grasp the full truth of their actions. When Jesus hung on the cross He prayed for forgiveness for those who crucified Him. He said, "Father, forgive them, for they know not what they do" (Luke 23:34). When Peter addressed a crowd of Jews in Solomon's Portico, he accused the Jews of killing Jesus, the Author of life, in ignorance (Acts 3:15, 17). In his letter to Timothy, Paul recounted his former life of unbelief and described himself as "a blasphemer, persecutor, and insolent opponent." However, he added, "But I received mercy because I had acted ignorantly in unbelief" (1 Timothy 1:13).

Undoubtedly millions of unbelievers today display ignorance of God by ridiculing believers and by not calling on God. The reason such people are still accountable for that is because such ignorance can be overcome (Psalm 19:1; Romans 1:18–20). They need to strip off their ignorance and trust in the Savior before it is too late.